Method of preparing stable dentifrice

ABSTRACT

1. A METHOD OF PREPARING A STABLE DENTIFRICE COMPRISING ADDING A WATER-SOLUBLE NON-TOXIC ACID ADDITION SALT OFF 1,6DI-(P-CHLOROPHENYL BIGUANIDO)HEXANE IN AMOUNTS OF ABOUT 0.01-5% BY WEIGHT OF THE FREE BASE THEREOF AND WATER TO A NON-AQUEOUS BLEND OF ABOUT 0.2-10% BY WEIGHT OF AN ALKALI METAL CARBOXMETHYL CELLULOSE AND A HUMECTANT, THEN ADDING A SURFACC-ACTIVE AGENT TO FORM A GEL AND THEN ADDING TO SAID GEL A DENTALLY ACCEPTABLE WATER-INSOLUBLE POLISHING MATERIAL; SAID PERCENTAGES BEING BASED ON SAID DENTIFRICE COMPOSITION.

Tinited States Patent O 3,842,168 METHOD OF PREPARING STABLE DENTIFRICEDaniel Colodney, Green Brook, N.J., assignor to Colgate- PalmoliveCompany, New York, N.Y. No Drawing. Continuation of abandonedapplication Ser. No. 126,922, Mar. 22, 1971. This application Jan. 15,

1973, Ser. No. 323,668

Int. Cl. A612: 7/16 US Cl. 424-52 9 Claims ABSTRACT OF THE DISCLOSUREMethod of stabilizing dentifrice containing alkali metal carboxyalkylcellulose and 1,6-di-(p-chlorophenyl biguanidohexane) salt againstprecipitation and floculation comprising adding to alkali metalcarboxyalkyl cellulose and a humectant, 1,6-di-(p-chlorophenylbiguanidohexane) in the form of a non-toxic water soluble salt thereof.Water is added together with or subsequent to the addition of the1,6-di-(p-chlorophenyl biguanidohexane) salt. Surface-active agent, suchas Sodium N-lauroyl sarcosinate is added to form a gel. The remainingdentifrice components including polishing agent are then added to thegel.

This is a continuation of application Ser. No. 126,922, filed Mar. 22,1971, and now abandoned.

This invention relates to a method of stabilizing a dentifrice againstprecipitation and floculation. More particularly, it relates tostabilization of a dentifrice composition which promotes oral hygiene.

In accordance with the method of the instant invention, a dentifricecontaining a water-soluble non-toxic acid addition salt of the highlydesirable antibacterial agent, 1,6-di- (p-chlorophenyl biguanidohexane),is provided. This anti bacterial agent is known to possess highlydesirable effect in inhibiting the growth of many microorganisms such asLactobacillus acidophilus odontolytz'cus and has, therefore, beenrecommended for incorporation into dentifrices.

However, the cosmetic stability of a dentifrice containing thisantibacterial agent and an alkali metal carboxyalkyl cellulose is notsatisfactory in view of incompatibility of these materials which leadsto precipitation and floculation in the dentifrice composition.

It is an advantage of the instant invention that a method of preparingthe stable dentifrice including a salt of 1,6-di- (p-chlorophenylbiguanidohexane) and alkali metal carboxyalkyl cellulose is provided.Other advantages of the invention will be apparent from consideration ofthe following specification.

In accordance with certain of its aspects, this invention relates to amethod of preparing a stable dentifrice comprising adding awater-soluble non-toxic acid addition salt of 1,6-di-(p-chlorophenylbiguanidohexane) and Water to an alkali metal carboxyalkyl cellulose anda humectant, then adding a surface-active agent to form a gel and thenadding to said gel a dentally acceptable water-insoluble polishingmaterial.

Any non-toxic Water-soluble salt of 1,6-di-(p-chlorophenylbiguanidohexane) antibacterial agent may be employed in the practice ofthe instant invention. The preferred acid addition salts are thegluconate, acetate, fluoride, dihydrogen fluoride and the like. Theantibacterial agent is employed in amount such that the gel containsabout 0.015-15 by Weight of the agent. Typically, the finisheddentifrice contains about 0.01% by weight, preferably about ODS-1% byweight of the agent. These amounts refer to the quantity of the freebase form of the agent.

Dentifrices such as tooth pastes or dental creams include a gellingagent. Alkali metal carboxyalkyl celluloses, and particularly sodiumcarboxymethyl cellulose,

3,842,168 Patented Oct. 15, 1974 are particuarly desirable gellingagents in dentifrices. In accordance with the method of this inventiondentifrices containing 1,6-di-(p-chlorophenyl blguanidohexane) salts andalkali metal carboxyalkyl cellulose are stabilized against precipitationand floculation.

The alkali metal carboxyalkyl cellulose is a hydrophilic colloid whichis soluble or dispersible in water and is generally classified as watersoluble. It is preferred to use the alkali metal salt of a carboxyalkylcellulose having up to three carbon atoms in the alkyl group, such asthe sodium and potassium salt of carboxymethyl cellulose. Sodiumcarboxymethyl cellulose and the like are available usually in the formof powders in various grades of purity and viscosity in solution.Commercial grades of sodium carboxymethyl cellulose having a purity fromabout 40 to on a dry basis and which are of low, medium or highviscosity may be important. The degree of substitution of thecarboxymethyl group per anhydroglucose unit in the cellulose molecule isvariable, but may be in the range from about 0.5 to 2. Another Watersoluble carboxyalkyl cellulose salt which may be important is sodiumcarboxyethyl cellulose. The carboxyalkyl cellulose agent is present inthe gel in amounts ranging from about 0.3%- 30% by weight of the gelpreferably 0.3 %15%. Typically, it is present in the finished dentifricein amount of about 02-10% and preferably about 0.25% by weight.

At the time the water-soluble, non-toxic salt of 1,6-di- (p-chlorophenylbiguanidohexane) is added to the alkali metal carboxyalkyl cellulosegelling agent, the gelling agent has been mixed with a humectant, suchas glycerine, sorbitol, propylene glycol and polyethylene glycol 400,including suitable mixtures thereof. Preferably the humectant isglycerine or a mixture of glycerine and sorbitol. The humectant contentis typically about 30%99% by weight of the gel preferably about 20%75 byweight of the finished dentifrice. The dentifrice typically containsabout 1535% by weight of glycerine.

Besides the Water-soluble, non-toxic acid addition salt of1,6-di(p-chlorophenyl blguanidohexane), water is also added to thealkali metal carboxyalkyl cellulose and the humectant. Water may beadded simultaneously with the salt of the antibacterial agent, orafterward. Whether it is preferred to dissolve the antibacterial agentsalt in the water and add the solution to the gelling agent and thehumectant, or to add the water after the antibacterial agent salt ismixed with the gelling and the humectant depends primarily on the formon which this salt is available; that is in solution or as solid. Thus,the gluconate is commercially available as a solution and when it isemployed, water is added subsequently to the mixing of the antibacterialagent digluconate with the mixing of the gelling agent and thehumectant. When the acetate or fluoride salt or the like, each of whichis commercially available as a solid, is employed, the salt is firstdissolved in water and slowly added to the alkali metal carboxyalkylcellulose and the humectant in solution. Water is typically employed inamount of about 22.5 %-69'.6% by weight, in the gel and about 15 %60% byweight of the finished dentifrice.

In the method of the instant invention the gel is formed by addingsynthetic organic surface active agent to the antibacterial agent,Water, gelling agent and humectant. Preferably the surface active agentacts in cooperation with the antibacterial agent to improve oralhygiene, assist in achieving thorough and complete dispersion of thecomponent of the dentifrice throughout the oral cavity, and render thedentifrice more cosmetically acceptable. When an anionic surface-activematerial is desired substantially saturated higher aliphatic acyl amidesof lower aliphatic amino, carboxylic acid compounds such as those having12 to 16 carbons in the fatty acid, alkyl or acyl radicals areparticularly preferred. Examples of the last mentioned amides areN-lauroyl sarcosine, and the sodium, potassium and ethanolamine salts ofN-lauroyl, N-myristoyl or N-palmitoyl sarcosine which should besubstantially free from soap or similar higher fatty acid material whichtends to substantially reduce the effect of these compounds. The use ofthese sarcosinate compounds in dentifrice compositions of the presentinvention is particularly advantageous since these materials exhibit aprolonged and marked effect in the inhibition of acid formation in theoral cavity due to carbohydrates breakdown in addition to exerting somereduction in the solubility of tooth enamel in acid solutions.

Other particularly suitable surface-active materials include nonionicagents such as condensates of sorbitan monostearate with approximately60 moles of ethylene oxide, condensates of ethylene oxide with propyleneoxide condensates of propylene glycol (available under the trademark(Pluronics)) and amphoteric agents such as quaternized imidazolederivatives which are available under the trademark Miranol such asMiranol C M. Cationic surface-active germicides and antibacterialcompounds such as di-isobutylphenoxyethyl dimethyl benzyl ammoniumchloride, benzyl dimethyl stearyl ammonium chloride, tertiary amines,having one fatty alkyl group (of from 12 to 18 carbon atoms) and two(poly) oxyethylene groups attached to the nitrogen (typically containinga total of from about 2 to 50 ethanoxy groups per molecule) and saltsthereof with acid and compounds of the structure where R is a fattyalkyl group containing from about 12 to 18 carbon atoms, and x, y, and ztotal 3 or higher, as well as salts thereof with mineral or organicacids, may also be used. It is preferred to use from about 0.075 to 15%by weight of the foregoing surface-active materials in the gel and about0.055% by weight in the dentifrice.

Any suitable substantially water-insoluble dentally acceptable polishingagent may be blended into the gel formed in the manner set forth above,thereby forming a dentifrice composition such as a toothpaste or cream,gel and the like. There is a relatively large number of such agentsknown in the art. Representative agents include, for example, dicaliciumphosphate, tricalcium phosphate, insoluble sodium metaphosphate,aluminum hydroxide, crystalline silica, magnesium carbonate, calciumcarbonate, calcium pyrophosphate, bentonites, etc., including suitablemixtures thereof. It is often desired to use an aluminum hydroxide, suchas the hydrated alumina sold by Alcoa as C333, and crystalline silicapolishing agents.

The polishing agent content is variable, but will generally be up toabout 75% by weight of the total composition, typically about 20-75%.

In the dentifrice, liquids and solids are apportioned to form a creamymass of desired consistency which is extrudable from an aerosolcontainer or a collapsible, e.g., aluminum or lead, tube.

Various other materials may be incorporated in the dentifrices of thisinvention. Examples thereof are coloring or whitening agents, silicones,chlorophyl compounds, ammoniated materials such as urea, and otherconstituents. These adjuvants are incorporated in the instantcompositions in amounts which do not substantially adversely affect theproperties and characteristics desired and are selected and used inproper amount depending upon the particular type of preparationinvolved. For example, ammoniated materials such as urea, and mixturesthereof, when present, are typically employed in amount of about 1 to 2%by weight.

In addition to 1,6-di- (p-chlorophenyl biguanidohexane), dentifrices inaccordance with this invention may in lude additional cationicantibacterial agents such as 4 N -(4-chlorobenzyD-N-(2,4-dichlorobenzyl) biguanide; p-chlorophenyl biguanide;4-chlorobenzhydryl biguanide; 4-chlorobenzhydrylguanylurea;N-3-lauroxpropyl-N -p-chlorobenzylbiguanide;

1 (lauryldimethylammonium 8 (p chlorobenzyldie methylammonium)) octanedichloride; 5,6-dichloro-2 guanidinobenzimidazole; N -p-chlorophenyl-N-laurylbiguanide;

5 amino 1,3 bis (2-ethy1hexyl)-5-methylhexahydropyrimidine;

and their non-toxic acid addition salts such as the gluconate andacetate. The total amount of such agents in cluding1,6-di(p-chlorophenyl biguanidohexane) is typically about 0.05 %5% byweight.

The dentifrice vehicle of the instant invention contains a flavoring oiland may also contain a sweetening agent. Examples of suitable flavoringoil include oils of spearmint, peppermint, Wintergreen, sassafras,clove, sage, eucalyptus, marjoram, cinnamon, lemon and orange, as wellas sodium methylsalicylate. Suitable sweetening agents include sucrose,lactose, maltose, sorbitol, sodium cyclamate, perillartine andsaccharine. Suitably, flavor alone or together with sweetening agent maytogether comprise from about 0.01 to 5% or more of the dentifrices ofthe instant invention. Sweetening agent may be adde prior to gelformation, as together with humectant, or after gel formation.

The compositions of the present invention suitably may also contain afluorine-containing compound having a beneficial effect on the care andhygiene of the oral cavity, e.g., diminution of enamel solubility inacid and protection of the teeth against decay. Examples thereof includesodium fluoride, potassium fluoride, potassium stannous fluoride (SnF-KF), sodium hexafluorostannate, stannous chlorofluoride, sodiumfluorozirconate, and sodium monofluorophosphate. These materials, whichdissociate or release fluorine-containing ions in water, suitably may bepresent in an effective but non-toxic amount, usually Within the rangeof about 0.01 to 1% by weight of the water soluble fluorine contentthereof.

The dentifrices should have a pH practicable for use. The pH range ofabout 5 to 9, preferably about 6-8, is considered the most practicablefor use. Where reference is made to pH herein, it is intended that suchpH determination be made on the gel directly.

The dentifrice of the invention may be further stabilized againstseparation into liquid and solid phases due to the presence of phosphateion and flavoring oil by including a stabilizing agent such as a Watersoluble alkaline earth metal salt of a strong acid, e.g. calciumchloride as described in Ser. No. 127,972 of Daniel Colodney and JamesNorfleet filed on even date herewith, or ethyl alcohol, as described inSer. No. 129,971 of Joseph Paul Jauuszewski and Tayseer George Bahouth,also filed on even date herewith.

The following specific examples are further illustrative of the natureof the present invention, but it is understood that the invention is notlimited thereto. The compositions are prepared in the usual manner andall amounts and proportions are by weight unless otherwise specified.

EXAMPLE 1 22.0 parts of glycerine and 0.20 parts of sodium saccharin areblended with 0.85 parts of sodium carboxymethyl cellulose.1,6-di-(p-chlorophenyl biguanidohexane) diacetate in amount providing0.5 parts of the free base form of the salt is dissolved in 16.65 partsof water and then slowly added with stirring to the blend of glycerine,sodium saccharine and sodium carboxymethyl cellulose. A gel is thenformed by adding to the above-mentioned materials 2.00 parts of sodiumN-lauroyl sarcosinate (35% water).

A dentifrice is then formed as 47.00 parts of dicalcium orthophosphatedihydrate, 5.00 parts of calcium carbonate, 5.0 parts of calciumchloride and 0.80 parts of oil of peppermint flavor are blended into thegel.

The dentrifrice thus formed remains cosmetically stable over an extendedperiod of time.

When the procedure set forth above is modified so that1,6-di-(p-chlorophenyl biguanidohexane) salt added to glycerine andsodium carboxymethyl cellulose in which water has been incorporated inthe conventional mode of preparation, the salt reacts with thecarboxymethyl cellulose resulting in precipitation and floculation inthe dentifrice.

EXAMPLE 2 The procedure of Example 1 is repeated except that 4.725 partsof a 20% solution of l,6-di-(p-chlorophenyl biguanidohexane) digluconateis added to the glycerine., sodium saccharine and sodium carboxymethylcellulose and water is thereafter added in total amount to 16.65 parts.

The completed dentifrice remains cosmetically stable over an extendedperiod of time.

It will be apparent to one skilled in the art that various modificationsmay be made and equivalents substituted therefor.

What is claimed is:

1. A method of preparing a stable dentifrice comprising adding awater-soluble non-toxic acid addition salt of 1,6- di-(p-chlorophenylbiguanido)hexane in amounts of about 0.0 l-5% by weight of the free basethereof and water to a non-aqueous blend of about 02-10% by weight of analkali metal carboxymethyl cellulose and a humectant, then adding asurface-active agent to form a gel and then adding to said gel adentally acceptable water-insoluble polishing material; said percentagesbeing based on said dentifrice composition.

2. The method claimed in Claim 1 wherein acid addition salt of1,6-di-(p-chlorophenyl biguanido)hexane is a salt selected from thegroup consisting of gluconate acetate, fluoride and dihydrogen fluoridesalts.

3. The method claimed in Claim 2 wherein said salt is1,6-di-(p-chlrophenyl biguanidohexane) diacetate and said salt is addedto the humectant and alkali metal carboxyalkyl in solution in water.

4. The method claimed in Claim 2 wherein said salt is 1,6-di-(p-chlorophenyl biguanido)hexane digluconate and said salt is added tothe humectant prior to the addition of water.

5. The method claimed in Claim 1 wherein said humectant is selected fromthe group consisting of glycerine, sorbitol, propylene glycol andpolyethylene glycol 400 and mixtures thereof.

6. The method claimed in Claim wherein said humectant is glycerine.

7. The method claimed in Claim 1 wherein said surfaceactive agent issodium N-lauroyl sarcosinate.

8. The method claimed in Claim 1 wherein based on 100% by weight of thedentifrice there are employed about 20-75% by weight of said humectant,about 0.2- 10% by weight of said alkali-metal carboxymethyl cellulose,about 0.0l5% by weight of said acid addition salt of1,6-di-(p-chlorophenyl biguanido)hexane, about 60% by weight of water,about 0.05-5% by weight of said surface-active agent and about -75% byWeight of said polishing material.

9. A method of preparing a stable dentifrice comprising adding awater-soluble non-toxic acid addition salt of 1,6-di-(p-chlorophenylbiguanido)hexane in amounts of about 0.01-5 of the free base thereof andwater to a non-aqueous blend of about 02-10% by weight of an alkalimetal salt of sodium carboxymethyl cellulose and a humectant comprisingglycerine, then adding sodium N-lauroyl sarcosinate to form a gel andthen adding to said gel a dentally acceptable Water-insoluble polishingmaterial; said percentages being based on said dentifrice composition.

References Cited FOREIGN PATENTS 825,577 12/1959 Great Britain 42454RICHARD L. HUF F, Primary Examiner U.S. CL. X.R. 42454

1. A METHOD OF PREPARING A STABLE DENTIFRICE COMPRISING ADDING AWATER-SOLUBLE NON-TOXIC ACID ADDITION SALT OFF 1,6DI-(P-CHLOROPHENYLBIGUANIDO)HEXANE IN AMOUNTS OF ABOUT 0.01-5% BY WEIGHT OF THE FREE BASETHEREOF AND WATER TO A NON-AQUEOUS BLEND OF ABOUT 0.2-10% BY WEIGHT OFAN ALKALI METAL CARBOXMETHYL CELLULOSE AND A HUMECTANT, THEN ADDING ASURFACC-ACTIVE AGENT TO FORM A GEL AND THEN ADDING TO SAID GEL ADENTALLY ACCEPTABLE WATER-INSOLUBLE POLISHING MATERIAL; SAID PERCENTAGESBEING BASED ON SAID DENTIFRICE COMPOSITION.